急性白血病患者静脉注射高剂量阿糖胞苷后血浆阿糖胞苷、阿糖尿苷、细胞内三磷酸阿糖胞苷浓度测定和影响因素分析

Determination of Ara-C in plasma and Ara-CTP in leukemic cells after intravenous infusion of highdose Ara-C in patients with acute leukemia and analysis of influence factors

目的 检测急性白血病患者静脉注射高剂量阿糖胞苷（Ara-C）后血浆、阿糖尿苷（Ara—U）和细胞内三磷酸阿糖胞苷（Ara—CTP）浓度，对不同Ara—C给药剂量和细胞内外药物浓度间的关系及影响因素进行分析研究。方法提取75例急性白血病患者首剂静脉注射不同剂量Ara—C（分别为0．5、1．0、2．0g／m2）后单个核细胞和血清，采用不同色谱条件进行反相高效液相色谱法（RP—HPLC）分析。结果细胞内Ara—CTP检测质量浓度在0．28～18，96μg／ml范周内线性关系良好（，=0．998），检测限为0．28μg／ml；血浆Ara—C和Ara—U的检测限分别为0．0157和1．034μg／ml；27例样本的保存时问超过1．5年，其中11例血浆Ara-C浓度低于检测限（40．7％），36例样本的单个核细胞数〈1．5×106／ml，其中15例细胞内Ara—CTP浓度低于检测限（41．7％）；血浆Ara．U和细胞内Ara—CTP浓度随给药剂量增加而增高，血浆Ara—C浓度未随给药剂量增加而增高；年龄〉40岁患者的细胞内Ara—CTP浓度有随年龄增长而增加的趋势.结论RP—HPLC法用于Ara—C血药浓度和细胞内Ara—CTP水平测定简便、稳定、重复性好。在Ara—C0．5～2．0g／m2剂量范围内，血浆Ara—u和细胞内Ara．CTP浓度随给药剂量增加而增高。

Objective To determine the plasma and intracellular concentration of Ara-C by the RP- HPLC method and analyse the influence factors and the relationship between the concentration and drug dose. Methods Mononuclear cells and serum of 75 patients with acute leukemia were extracted after the first intravenous infusion of different administration dosage of Ara-C （0.5, 1.0, 2.0 g/m2）, and analysed with different chromatographic conditions by RP-HPLC. Results The linear range of Ara-CTP was 0.28-18.96 μg/ ml （r =0.998）, and the dqtection limit was 0.28 μg/ml. The detection limit of Ara-C and Ara-U in plasma was 0.0157 μg/ml and 1.034 μg/ml respectively. In 27 samples preserved for more than 1.5 years, 11 （40.7 %） cases of the plasma concentration of Ara-C were below the detection limit.In 36 samples of mononuclear cell count below 1.5×106/ml, 15 cases （41.7 %） of intracellular concentration of Ara-CTP were below the detection limit. The plasma concentration of Ara-U and intracellular concentration of Ara-CTP were increased with administration dosage of Ara-C increased, and the plasma concentration of Ara-C was not increased. The intracellular concentration of Ara-CTP in old patients over 40 years was tend to in crease with age. Conclusion The RP-HPLC method is simple, rapid, stable, reproducible and applicable for the monitoring of the plasma concentration of Ara-C and intracellular concentration of Ara-CTP. In 0.5-2.0 g/m2 dose range of Ara-C, the plasma concentration of Ara-U and intracellular concentration of Ara-CTP was increased with administration dosage of Ara-C increased.